Abstract 2652: Bivalirudin During Early Invasive Strategy for Acute Coronary Syndromes: Noninferiority in ACUITY Lies in the Eyes of the Beholder
Background: A non-inferiority (NI) trial, ACUITY, concluded that bivalirudin (Bv) alone or Bv+glycoprotein 2b/3a inhibitor (GPI) (new treatment) is noninferior to heparin/enoxaparin (Hep/Enox) +GPI (standard treatment) in preventing ischemic complications in patients undergoing early invasive strategy for acute coronary syndromes (ACS).
Objective: To perform NI analysis with regards to efficacy (E) and efficacy + safety (E+S) using a conservative NI margin, and compare it with ACUITY, where a liberal margin (chosen on the basis of expert consensus within the trial committee) was employed (a risk ratio (RR) of 1.25).
Methods: The conservative NI margin (d) was derived as 50% of the 95% lower limit (dmax) of random-effects meta-analytic CI of RR for historical trials (EPISTENT & ESPRIT) comparing Hep (placebo) vs GPI+Hep (Historical RR). NI is established if 95% upper limit of CI of new vs standard treatment (Observed RR) <NI margin.
Results (Table⇓): NI for E is established using the liberal margin (dmax) for Bv and Bv+GPI. Using the more conservative margin (d), NI cannot be inferred for E. NI for E+S is established using both margins for Bv, but not for Bv+GPI. Superiority in terms of E+S is driven in favor of Bv vs Hep/Enox+GPI by a greater difference in safety (47% risk reduction) compared to efficacy (8% risk increase). In contrast, NI is established for all comparisons using ACUITY’s liberal margin.
Conclusions: Despite the ACUITY investigators’ claims to the contrary we conclude that neither Bv nor Bv+GPI has been shown to be noninferior to Hep/Enox+GPI during early invasive strategy for ACS with respect to efficacy using conservative interpretive criterion. These analyses are consistent with those based on REPLACE-2 trial and call into question the enthusiastic claims that Bv should be the antithrombotic agent of choice during elective or non-elective PCI.